Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial.
ABSTRACT: Background:COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. Study design and methods:This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.
Project description:<h4>Purpose</h4>Low-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia.<h4>Materials and methods</h4>We conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ?50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT.<h4>Results</h4>Nine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia.<h4>Conclusions</h4>Our preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.
Project description:Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease which can lead to acute respiratory distress syndrome requiring ventilatory support and intensive care unit admission. The aim of our study is to evaluate the performance of two non-invasive respiratory function indices (the ROX index and the SatO2/FiO2 ratio), as compared to the traditional PaO2/FiO2 ratio, in predicting a clinically relevant composite outcome (death or intubation) in hospitalized patients for COVID-19 pneumonia. Four hospital centers in Northern Italy conducted an observational retrospective cohort study during the first wave of COVID-19 pandemic. Four hundred and fifty-six patients with COVID-19 pneumonia admitted to medical or sub-intensive wards were enrolled. Clinical, laboratory, and respiratory parameters, for the calculation of different indices, were measured at hospital admission. In medical wards (Verona and Padua) the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio were able to predict intubation or death with good accuracy (AUROC for the PaO2/FiO2 ratio, ROX index and SatO2/FiO2 ratio of 75%, 75% and 74%, respectively). Regarding sub-intensive wards (Milan and Mantua), none of the three respiratory function indices was significantly associated with the composite outcome. In patients admitted to medical wards for COVID-19 pneumonia, the ROX index and the SatO2/FiO2 ratio demonstrated not only good performance in predicting intubation or death, but their accuracy was comparable to that of the PaO2/FiO2 ratio. In this setting, where repeated arterial blood gas tests are not always feasible, they could be considered a reliable alternative to the invasive PaO2/FiO2 ratio.